Directing Biosynthesis VI - Book of abstracts

Investigating bioactive natural products from the fungus Escovopsis weberi Claudio Greco, Matt I. Hutchings and Barrie Wilkinson John Innes Centre, UK New sources of bioactive molecules are required in the hunt for new chemical diversity to address the current antimicrobial resistance (AMR) crisis. Despite most antibiotics deriving from natural products, discovery efforts have focused on only a small section of the tree of life. Under-exploited sources of bioactive compounds include highly specialized fungi evolving in competitive environments: an excellent example is the ant-nest pathogen Escovopsis weberi . Garden ants (Acromyrmex) live in symbiosis with the garden fungus Leucoagaricus gongylophorus and Pseudonocardia bacteria that grow on the ant cuticle and produce anti-infective molecules which help protect the fungus garden from infection. This tight mutualistic relationship prevents invasion by the co-evolved pathogen E. weberi , which can cause ant colony collapse. 1,2 Bioinformatics analysis of E. weberi genomes revealed 26 biosynthetic gene clusters (BGCs), most of which are unique to E. weberi . Heterologous expression system is being optimised for the production of compounds from these unique BGCs. Metabolomics analysis identified uncharacterised metabolites produced on rice and oats cultures, which are being purified and tested for different activities References 1. F. D Batey, C Greco, M. I. Hutchings & B. Wilkinson, 2020, Curr. Opin. Chem. Biol . 59 , 172-181. 2. Heine, N. A Holmes, A. C. A. Santos, T. M. Innocent, K. Scherlach, E. H. Patrick, D. W. Yu, J. C. Murrell, P. C. Vieria, J. J. Boomsma, C. Hertweck, M. I. Hutchings & B. Wilkinson, 2018, Nat. Commun . 9 , 2208.

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